Cartilage-targeting and inflammatory-responsive nanocarriers for effective osteoarthritis treatment via reactive oxygen species scavenging and anti-angiogenesis

Osteoarthritis(OA),a common disabling joint disease,is highly associated with microenvironmental changes in the cartilage and subchondral bone.Elevated reactive oxygen species(ROS)in the cartilage and subchondral bone angiogenesis accelerate articular cartilage erosion.New cartilage-targeting drug deliv-ery systems that are aimed at preventing ROS production and angiogenesis may be of clinical significance for OA treatment.Herein,an ROS scavenger and an inflammatory-responsive nanocarrier are designed by immobilizing the natural polyphenol(curcumin)in chitosan-catechol nanoformulations(Cur-CS-C NPs)via boronate ester.The robust cartilage-targeting effects and ROS scavenging capacities of Cur-CS-C NPs were respectively determined in cartilage explants and chondrocytes.Intra-articular injection of Cur-CS-C NPs in OA rat models efficiently suppressed angiogenesis and cartilage degradation partially via the ROS-mediated NF-κB/PI3K-Akt signaling pathway.The developed curcumin-functionalized nanocarriers can significantly delay OA progression and provide a promising therapeutic strategy for other inflamma-tory diseases that are characterized by oxidative stress and angiogenesis.